Inhibiting heat shock factor 1 in human cancer cells with a potent RNA aptamer.
Inhibiting heat shock factor 1 in human cancer cells with a potent RNA aptamer.
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DOI:
10.1371/journal.pone.0096330
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Lis JT
中科院分区:
文献类型:
--
作者:
Salamanca HH;Antonyak MA;Cerione RA;Shi H;Lis JT
Heat shock factor 1 (HSF1) is a master regulator that coordinates chaperone protein expression to enhance cellular survival in the face of heat stress. In cancer cells, HSF1 drives a transcriptional program distinct from heat shock to promote metastasis and cell survival. Its strong association with the malignant phenotype implies that HSF1 antagonists may have general and effective utilities in cancer therapy. For this purpose, we had identified an avid RNA aptamer for HSF1 that is portable among different model organisms. Extending our previous work in yeast and Drosophila, here we report the activity of this aptamer in human cancer cell lines. When delivered into cells using a synthetic gene and strong promoter, this aptamer was able to prevent HSF1 from binding to its DNA regulation elements. At the cellular level, expression of this aptamer induced apoptosis and abolished the colony-forming capability of cancer cells. At the molecular level, it reduced chaperones and attenuated the activation of the MAPK signaling pathway. Collectively, these data demonstrate the advantage of aptamers in drug target validation and support the hypothesis that HSF1 DNA binding activity is a potential target for controlling oncogenic transformation and neoplastic growth.
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影响因子:
6.5
作者:
Richardson PG;Badros AZ;Jagannath S;Tarantolo S;Wolf JL;Albitar M;Berman D;Messina M;Anderson KC
通讯作者:
Anderson KC
DOI:
10.1158/1078-0432.ccr-13-0477
发表时间:
2013-09-01
期刊:
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子:
--
作者:
Hong D;Said R;Falchook G;Naing A;Moulder S;Tsimberidou AM;Galluppi G;Dakappagari N;Storgard C;Kurzrock R;Rosen LS
通讯作者:
Rosen LS
DOI:
10.1073/pnas.88.16.6911
发表时间:
1991-08-01
影响因子:
11.1
作者:
SCHUETZ, TJ;GALLO, GJ;KINGSTON, RE
通讯作者:
KINGSTON, RE
影响因子:
64.5
作者:
Dai, Chengkai;Whitesell, Luke;Lindquist, Susan
通讯作者:
Lindquist, Susan
影响因子:
11.2
作者:
Sawai, Ayana;Chandarlapaty, Sarat;Solit, David B.
通讯作者:
Solit, David B.